Major interaction on record — check this product against your medications before combining. Based on 21 of 24 ingredients. Check your meds →
Dietary supplement

Cir-Q Tonic Ingredients & Drug Interactions

by VerVita

Cir-Q Tonic label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Cir-Q Tonic against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Cir-Q Tonic is a dietary supplement by VerVita with 24 active ingredients. Its ingredients are commonly taken for preventing or treating thiamine deficiency, beriberi, wernicke-korsakoff syndrome (alcohol-related).Based on those ingredients, 1,483 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Vitis vinifera (Grape) extract, Beta vulgaris, Echinacea purpurea extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Cir-Q Tonic by VerVita

Ask about any prescription or over-the-counter medication and we check it for interactions with Cir-Q Tonic by VerVita — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Cir-Q Tonic by VerVita

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 12, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 16 of its 24 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (310 mg) without saying how much of each component you get.

Cir-Q Tonic contains 24 active ingredients chosen to support cardiovascular function and nutrient status. The formula includes B vitamins (thiamine, biotin, pantothenic acid, riboflavin, vitamin B6, vitamin B12) that support energy and nerve health; minerals (iron, selenium, manganese, chromium, molybdenum, vanadium, and rubidium) that play roles in metabolism and enzyme function; fat-soluble vitamins A, D, and C for immune and antioxidant support; coenzyme Q10 for cellular energy; and plant extracts from grape, buckwheat, and echinacea for additional phytonutrient content.

Tocotrienols (a form of vitamin E) round out the antioxidant profile. The product also contains inactive ingredients including a trace mineral complex, magnesium, and a vegetarian capsule.

Does it work?

Strong evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Anemia of chronic disease — rated "Effective" (Iron) (Natural Medicines).
  • On file: Sideroblastic anemia — rated "Effective" (Vitamin B6) (Natural Medicines).
  • On file: Familial hypophosphatemia — rated "Effective" (Vitamin D) (Natural Medicines).
  • On file: Imerslund-Grasbeck disease — rated "Effective" (Vitamin B12) (Natural Medicines).
  • On file: Iron deficiency anemia — rated "Effective" (Iron) (Natural Medicines).

The evidence for this multi-ingredient formula varies by component. Some ingredients are well-established — thiamine for thiamine deficiency and Wernicke-Korsakoff syndrome, vitamin D for bone and mineral disorders, and iron for iron-deficiency anemia.

Others show promise but need stronger evidence: coenzyme Q10 for heart function and migraines, grape extract for circulation, and selenium for thyroid and immune health. Still others lack clear proof — for example, vitamin B6 is possibly effective for pregnancy-related nausea, but many claimed uses of the botanical extracts (echinacea for general immunity, buckwheat for blood sugar) are rated as having insufficient evidence.

Because this is a combination product targeting general wellness rather than a specific deficiency or disease, the product facts we hold do not establish an overall effectiveness rating for Cir-Q Tonic as a whole.

The evidence, ingredient by ingredient Thiamine Biotin Vanadium Grape Buckwheat Beet Tocotrienols Echinacea

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 21 of the 21 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 21 of 21.
  • General safety write-ups exist for 21 of 21.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Overall, the individual ingredients in Cir-Q Tonic are generally well tolerated when used as directed. B vitamins (thiamine, biotin, pantothenic acid, riboflavin, vitamin B12) are considered safe; excess is excreted in urine.

Vitamin D is safe at recommended doses but can cause toxicity at very high intakes. Iron may cause nausea, constipation, or diarrhea in some people.

Vitamin C at high doses (above 2 grams daily) can cause diarrhea and stomach upset. Selenium, chromium, vanadium, and manganese are safe in normal amounts but can cause problems at high doses — selenium excess can damage organs, manganese at high intake poses nerve damage risk, and vanadium can harm the kidneys.

For pregnancy and lactation, most ingredients are considered likely safe at normal amounts, though high-dose vitamin A (retinol) should be avoided in pregnancy due to birth-defect risk. Thiamine, pantothenic acid, vitamin B12, and coenzyme Q10 are needed during pregnancy and breastfeeding.

Vanadium and tocotrienols lack sufficient safety data for pregnancy; discuss high-dose supplementation with your doctor.

Side effects, ingredient by ingredient Thiamine Biotin Vanadium Grape Buckwheat Beet Tocotrienols Echinacea

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 17 of the 21 matched ingredients can interact with medications — Manganese, Beet, Grape, Vanadium, Iron, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; Parkinson's medications.
  • For scale: 1,484 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Cir-Q Tonic, check with your pharmacist if you use any of the following: retinoid medications (tretinoin, isotretinoin — major interaction with vitamin A); anticoagulants or blood thinners like warfarin, apixaban, or clopidogrel (interact with vitamin D, selenium, grape extract, echinacea, tocotrienols); heart-rhythm drugs such as verapamil, diltiazem, or digoxin (vitamin D); thiazide diuretics for blood pressure (vitamin D); cholesterol drugs like atorvastatin (vitamin D); antibiotics including quinolones, tetracyclines (iron, manganese); blood-pressure medications (vitamin B6, coenzyme Q10, beet); seizure medications like phenobarbital or phenytoin (vitamin B6); thyroid medication levothyroxine (iron, chromium, vitamin C); diabetes and insulin drugs (chromium, vanadium); immunosuppressants (selenium, echinacea); and any chemotherapy. No interactions are documented for the ingredients we could not check (folate, bioflavonoids, rubidium).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with strong clinical evidence behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.

Cir-Q Tonic is a broad-spectrum nutrient and plant-extract formula that may appeal to people seeking general cardiovascular and metabolic support. However, because it contains 24 ingredients with documented interactions across nearly 1,500 individual medications — including serious ones with retinoids, anticoagulants, diabetes and blood-pressure drugs, and thyroid medication — you absolutely must check your exact medications using the tool below before starting.

If you take prescription medications, especially for the heart, blood thinning, or hormone-related conditions, talk with your pharmacist first.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 21 of 24 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 26, 2020.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Cir-Q Tonic, straight from the product label.

Brand VerVita
Net contents 90 Capsule(s)
Market status On market
Date entered into DSLD Feb 26, 2020
DSLD ID 213618
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses Nutrient, All Other
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Cir-Q Tonic by VerVita, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
Servings per container
90
IngredientAmount% DV
Thiamine5 mg333%
Biotin5 mcg2%
Proprietary Blend310 mg--
Pantothenic Acid5 mg50%
Vitamin D3300 IU75%
Iron2 mg11%
Vitamin B125 mcg83%
Selenium5 mcg7%
Vitamin C10 mg17%
Vanadium0 NP--
Manganese4.5 mg225%
Vitamin B65 mg250%
Chromium25 mcg21%
Molybdenum10 mcg13%
Vitamin A1500 IU30%
Folate5 mcg1.25%
Riboflavin 5'-Phosphate5 mg294%
Coenzyme Q1025 mg--
Vitis vinifera (Grape) extract0 NP--
Polygonum fagopyrum (Buckwheat) extract0 NP--
Beta vulgaris0 NP--
Tocotrienols0 NP--
Echinacea purpurea extract0 NP--
Bioflavonoids0 NP--
Rubidium0 NP--

Other ingredients: natural Trace Mineral Complex, Vegetarian Capsule, Magnesium

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Suggested/Recommended/Usage/Directions

Recommendation: Take one (1) capsule per day as a dietary supplement or as otherwise directed by a healthcare professional.

Precautions

Keep out of reach of children.

Sealed with a safety seal for your protection.

Warning: Accidental overdose of iron-containing products is a leading cause of poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

Storage

Store in a cool, dry area.

FDA Statement of Identity

Dietary Supplement

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Cir-Q Tonic by VerVita label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Cir-Q Tonic label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Cir-Q Tonic by VerVita

These are the 24 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Servings per container90 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Thiamine

Interacts with
3 drugs
5 mg per serving Form: Vitamin B1

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get eno...

Thiamine monograph & interactions

Biotin

No known
interactions
5 mcg per serving

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get...

Biotin monograph & interactions

Proprietary Blend

310 mg per serving

Pantothenic Acid

No known
interactions
5 mg per serving

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nea...

Pantothenic Acid monograph & interactions

Vitamin D3

Interacts with
715 drugs
300 IU per serving Form: Cholecalciferol

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people,...

Vitamin D3 monograph & interactions

Iron

Interacts with
80 drugs
2 mg per serving Form: Iron Amino Acid Chelate

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventin...

Iron monograph & interactions

Vitamin B12

Interacts with
20 drugs
5 mcg per serving Form: Methylcobalamin

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...

Vitamin B12 monograph & interactions

Selenium

Interacts with
321 drugs
5 mcg per serving Form: L-Selenomethionine

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...

Selenium monograph & interactions

Vitamin C

Interacts with
207 drugs
10 mg per serving Form: L-Ascorbic Acid

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Manganese

Interacts with
83 drugs
4.5 mg per serving Form: Manganese Gluconate

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get...

Manganese monograph & interactions

Vitamin B6

Interacts with
210 drugs
5 mg per serving Form: Pyridoxal 5-Phosphate

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

Chromium

Interacts with
178 drugs
25 mcg per serving Form: Chromium Amino Acid Chelate

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control i...

Chromium monograph & interactions

Molybdenum

No known
interactions
10 mcg per serving Form: Molybdenum Amino Acid Chelate

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so s...

Molybdenum monograph & interactions

Vitamin A

Interacts with
387 drugs
1500 IU per serving Form: Mixed Carotenoids

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplemen...

Vitamin A monograph & interactions

Folate

5 mcg per serving Form: L-Methylfolate

Riboflavin 5'-Phosphate

Interacts with
20 drugs
5 mg per serving

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally...

Riboflavin 5'-Phosphate monograph & interactions

Coenzyme Q10

Interacts with
198 drugs
25 mg per serving Form: Ubiquinone

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated...

Coenzyme Q10 monograph & interactions

Other (inactive) ingredients: Natural Trace Mineral Complex, Vegetarian Capsule, Magnesium. These complete the product’s ingredient list but are not active constituents.

Interaction report

Cir-Q Tonic by VerVita Drug Interactions

Want to check YOUR meds against Cir-Q Tonic?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,483Drugs
9 Major 1,434 Moderate 40 Minor

Ingredients driving the most interactions

Vitis vinifera (Grape) extract 910
Beta vulgaris 861
Echinacea purpurea extract 816
Vitamin D3 715
Vitamin A 387

Individual Drug Interactions

The ingredients in Cir-Q Tonic interact with 1,483 drugs. Click any drug to see the details.

17 of the 24 ingredients in Cir-Q Tonic interact with drugs. Each result below shows which ingredient is responsible. Vitis vinifera (Grape) extract Beta vulgaris Echinacea purpurea extract Vitamin D3 Vitamin A Selenium Vitamin B6 Vanadium Vitamin C Coenzyme Q10 Chromium Tocotrienols Manganese Iron Vitamin B12 Riboflavin 5'-Phosphate Thiamine

Each ingredient & the kinds of drugs it affects

For each ingredient in Cir-Q Tonic with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Vitis vinifera (Grape) extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

Likelihood Possible Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

Likelihood Possible Evidence B
Cytochrome P450 2C9 (Cyp2C9) Substrates

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D
Vitis vinifera (Grape) extract full monograph & interactions

Beta vulgaris3 drug types · 861 drugs

Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, beet might increase the levels of CYP3A4 substrates.
In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole.

Likelihood Possible Evidence D
Antihypertensive Drugs

Beet and beetroot contain nitrates, which can cause vasodilation, potentially leading to lower blood pressure. However, a study published in the European Journal of Clinical Nutrition using concentrated beetroot juice found no significant impact on blood pressure or heart rate in different age groups. Other small clinical studies suggest that while beet consumption might transiently lower blood pressure due to vessel dilation, there's no consistent evidence of a lasting effect. Overall, the theoretical risk of reduced blood pressure due to beet's nitrate content exists, but studies generally indicate a low and temporary impact rather than a sustained decrease.

Likelihood Possible Evidence A
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research suggests that beet induces CYP1A2 enzymes.

Likelihood Possible Evidence D
Beta vulgaris full monograph & interactions

Echinacea purpurea extract12 drug types · 816 drugs

Caffeine

Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
Echinacea seems to increase plasma concentrations of caffeine by around 30%. This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30%. Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.

Likelihood Possible Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir. However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4. The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4. In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate.

Likelihood Possible Evidence B
Etoposide (Vepesid)

Echinacea may increase levels of etoposide.
In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism. Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme.

Likelihood Possible Evidence D
Immunosuppressants

Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.
Theoretically, echinacea may interfere with immunosuppressant therapy because of its immunostimulant activity.

Likelihood Possible Evidence B
Darunavir (Prezista)

Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.
Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients.

Likelihood Unlikely Evidence B
Dayquil Severe

Echinacea is reported to have varying effects on a number of Cytochrome P450 metabolizing enzymes in the liver, including CYP1A2 and CYP3A4, which play a role in acetaminophen and dextromethorphan metabolism (both contained in DayQuil Severe), respectively. Studies have reported both enzyme inhibition and induction, making it difficult to predict clinically significant drug interactions with reliability. Specific drug interaction studies reporting definitive results are rare, and potential drug interactions involving echinacea should likely be taken on a case-by-case basis. Based on what we know about how acetaminophen and dextromethorphan are metabolized, the risk of a clinically significant interaction between echinacea and DayQuil Severe is low.

Likelihood Unlikely Evidence A
Docetaxel (Taxotere)

Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.
Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study.

Likelihood Unlikely Evidence B
Etravirine (Intelence)

Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.
Etravirine is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg three times daily for 14 days did not alter the pharmacokinetics of etravirine in HIV-infected patients.

Likelihood Unlikely Evidence B
Lopinavir/Ritonavir (Kaletra)

Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.
Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers.

Likelihood Unlikely Evidence B
Midazolam (Versed)

Theoretically, echinacea may increase the metabolism of intravenous midazolam.
Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam. Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.
Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR.

Likelihood Possible Evidence B
Echinacea purpurea extract full monograph & interactions

Vitamin D38 drug types · 715 drugs

Aluminum

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Likelihood Probable Evidence B
Thiazide Diuretics

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Likelihood Probable Evidence D
Verapamil (Calan, Others)

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

Likelihood Probable Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Likelihood Possible Evidence D
Vitamin D3 full monograph & interactions

Vitamin A4 drug types · 387 drugs

Retinoids

Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.
Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements.

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.
The tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk of adverse effects. Doses of vitamin A above the UL can cause hepatotoxicity, ranging from elevated liver enzymes to liver failure.

Likelihood Possible Evidence C
Tetracycline Antibiotics

Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.
Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition. Avoid high doses of vitamin A in people taking tetracyclines chronically.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.
Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism. Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.

Likelihood Possible Evidence D
Vitamin A full monograph & interactions

Selenium6 drug types · 321 drugs

Anticoagulant/Antiplatelet Drugs

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Likelihood Possible Evidence D
Barbiturates

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Likelihood Possible Evidence D
Contraceptive Drugs

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Likelihood Possible Evidence B
Niacin

Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Selenium full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Vanadium2 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, vanadium might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
In vitro research shows that the sodium orthovanadate form of vanadium prolongs clotting time, likely through inhibition of thrombin and factor Xa.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, vanadium might increase the risk of hypoglycemia when taken with antidiabetes drugs.
A few very small clinical studies in patients with type 2 diabetes show that the vanadyl sulfate form of vanadium increases insulin sensitivity and might lower blood glucose levels.

Likelihood Probable Evidence B
Vanadium full monograph & interactions

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Vitamin C full monograph & interactions

Coenzyme Q103 drug types · 198 drugs

Alkylating Agents

Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.
Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy. The clinical importance of this interaction is unknown.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.
Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin. Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported. However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.
Some clinical research shows that coenzyme Q10 can significantly lower blood pressure, although other studies have shown conflicting results.

Likelihood Possible Evidence B
Coenzyme Q10 full monograph & interactions

Chromium5 drug types · 178 drugs

Antidiabetes Drugs

Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes.

Likelihood Possible Evidence A
Insulin

Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
In clinical research, chromium has been shown to increase insulin sensitivity,

Likelihood Possible Evidence B
Levothyroxine (Synthroid, Others)

Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone. Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

Likelihood Probable Evidence B
Aspirin

Theoretically, aspirin might increase chromium absorption.
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood.

Likelihood Possible Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

NSAIDs might increase chromium levels in the body.
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention.

Likelihood Possible Evidence D
Chromium full monograph & interactions

Tocotrienols1 drug type · 122 drugs

Anticoagulant/Antiplatelet Drugs

Concomitant use of tocotrienols with anticoagulant or antiplatelet agents might increase the risk of bleeding. However, this has not been reported in humans.
Taking tocotrienols orally inhibits experimentally-induced platelet aggregation in humans. Theoretically tocotrienols might increase the risk of bleeding if taken with antiplatelet or anticoagulant drugs. However, tocotrienols 400-800 mg daily have been used with aspirin and/or clopidogrel for 1 year with no clear cumulative antiplatelet effects and no reports of bleeding.

Likelihood Unlikely Evidence B
Tocotrienols full monograph & interactions

Manganese3 drug types · 83 drugs

Antipsychotic Drugs

Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Manganese full monograph & interactions

Iron13 drug types · 80 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Iron might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and iron can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, iron containing products.

Likelihood Probable Evidence D
Bisphosphonates

Iron reduces the absorption of bisphosphonates.
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Denosumab (Prolia, Others)

Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other.

Likelihood Possible Evidence D
Dolutegravir (Tivicay)

Iron might decrease dolutegravir levels by reducing its absorption.
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54%.

Likelihood Probable Evidence B
Integrase Inhibitors

Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation. One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation. Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation.

Likelihood Possible Evidence D
Levodopa

Iron might decrease levodopa levels by reducing its absorption.
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50%. The clinical significance of this hasn't been determined.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Iron might decrease levothyroxine levels by reducing its absorption.
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence B
Methyldopa (Aldomet)

Iron might decrease methyldopa levels by reducing its absorption.
Advise patients to separate methyldopa and iron doses by at least 2 hours. Iron can decrease the absorption of methyldopa from the gastrointestinal tract through chelation, resulting in increases in blood pressure.

Likelihood Probable Evidence B
Mycophenolate Mofetil (Cellcept)

Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research.

Likelihood Unlikely Evidence D
Penicillamine (Cuprimine, Depen)

Iron might decrease penicillamine levels by reducing its absorption.
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine.

Likelihood Probable Evidence D
Quinolone Antibiotics

Iron might decrease levels of quinolone antibiotics by reducing their absorption.
Advise patients to separate quinolone antibiotics and iron doses by at least 2 hours. Iron decreases the absorption of quinolones due to formation of insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90%.

Likelihood Probable Evidence D
Chloramphenicol

Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Chloramphenicol interferes with erythrocyte maturation. However, since chloramphenicol isn't usually taken for prolonged periods, this isn't likely to be clinically significant.

Likelihood Unlikely Evidence D
Iron full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions

Riboflavin 5'-Phosphate1 drug type · 20 drugs

Tetracycline Antibiotics

Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

Likelihood Possible Evidence D
Riboflavin 5'-Phosphate full monograph & interactions

Thiamine1 drug type · 3 drugs

Trimethoprim (Proloprim)

Trimethoprim might increase blood levels of thiamine.
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations.

Likelihood Probable Evidence B
Thiamine full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Cir-Q Tonic, from the product label.

VerVita

See all VerVita products
Name
VerVita Products, LLC
City
Grand Rapids
State
MI
ZipCode
49534
Phone Number
616.453.2306
Web Address
www.VerVitaProducts.com
Pharmacist Counseling Corner

Cir-Q Tonic by VerVita: Common Questions

Does Cir-Q Tonic by VerVita interact with any medications?
Yes. Based on its ingredients, Cir-Q Tonic has a known interaction with 1,483 medications, including 9 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Cir-Q Tonic contains 24 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is Cir-Q Tonic safe to take if I'm pregnant?
Most ingredients are likely safe at the amounts typically found in supplements, and several (thiamine, B12, folate, vitamin D) are actually needed in pregnancy. However, high-dose vitamin A (retinol) can harm fetal development, and vanadium and tocotrienols lack enough safety data. Talk with your doctor or midwife before starting any supplement in pregnancy — they can review the exact dose in this product against your individual needs.
Can I take this while breastfeeding?
Most ingredients — B vitamins, vitamin C, vitamin D, and coenzyme Q10 — are considered safe and even beneficial while nursing at recommended levels. However, some ingredients have limited safety data while breastfeeding, including echinacea, tocotrienols, grape extract, and manganese (which may carry additional risks). Check with your doctor before taking high-dose versions or extended use.
What does coenzyme Q10 do in this formula?
Coenzyme Q10 (CoQ10) is a compound your cells use to produce energy. It's possibly effective for heart function and migraine headaches, and research suggests it may support muscle and energy metabolism. Your body makes its own CoQ10, but levels can decline with age or with certain medications.
Why are there so many minerals in this product?
Minerals like selenium, chromium, manganese, iron, and vanadium are cofactors in hundreds of enzyme reactions that keep metabolism, thyroid function, blood sugar control, and immune health on track. This formula combines them to support overall nutrient status, though the evidence for using them together as a 'tonic' rather than treating specific deficiencies is not established in the data we hold.
Will this product help my heart?
Some ingredients — coenzyme Q10, vitamin D, and the plant extracts like grape — have research suggesting benefits for circulation and heart-related conditions. However, this product is a general nutritional supplement, not a heart medication. If you have heart disease, ask your doctor whether this formula is appropriate for you and whether it might interact with your medications.
Is there iron in this if I have hemochromatosis?
Yes, iron is listed as an active ingredient. If you have hemochromatosis (high iron stores) or iron overload, you should avoid this product unless your doctor explicitly approves it. Taking extra iron when your body already stores too much can be harmful.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Not sure if Cir-Q Tonic is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Cir-Q Tonic label
Go deeper

The Full Monographs Behind Cir-Q Tonic’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Thiamine

Interacts with 3 drugs

Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get enough from food, but supplements are clear...

Read the full Thiamine monograph → Herb & supplement monograph

Biotin

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get plenty from a normal diet, and true defi...

Read the full Biotin monograph → Herb & supplement monograph

Vanadium

Interacts with 208 drugs

Vanadium is a trace mineral found in tiny amounts in food, and people get plenty from a normal diet. Supplement claims for diabetes, weight, and athletic performance are not well proven, and...

Read the full Vanadium monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph → Herb & supplement monograph

Buckwheat

Buckwheat is a nutritious, naturally gluten-free seed that is high in fiber, protein, and antioxidants like rutin. As a food it can be part of a heart-healthy diet, but evidence that buckwhe...

Read the full Buckwheat monograph → Herb & supplement monograph

Beet

Interacts with 861 drugs

Beet, especially beetroot juice, is a nitrate-rich food that may modestly lower blood pressure and slightly improve exercise performance in some people. It is generally safe as a food, but s...

Read the full Beet monograph → Herb & supplement monograph

Tocotrienols

Interacts with 122 drugs

Tocotrienols are a less common form of vitamin E with strong antioxidant activity studied mostly for cholesterol, liver, and heart health. Early research is interesting but far from conclusi...

Read the full Tocotrienols monograph → Herb & supplement monograph

Echinacea

Interacts with 816 drugs

Echinacea is a popular herb taken to help prevent or shorten the common cold, but study results are mixed and the overall benefit appears small at best. It is generally well tolerated for sh...

Read the full Echinacea monograph → Herb & supplement monograph

Pantothenic Acid

Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nearly all foods, and most people meet thei...

Read the full Pantothenic Acid monograph → Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...

Read the full Vitamin D monograph → Herb & supplement monograph

Iron

Interacts with 80 drugs

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventing iron deficiency and iron-deficiency an...

Read the full Iron monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 monograph → Herb & supplement monograph

Selenium

Interacts with 321 drugs

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...

Read the full Selenium monograph → Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph → Herb & supplement monograph

Manganese

Interacts with 83 drugs

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get enough from a normal diet. Supplements m...

Read the full Manganese monograph → Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

Chromium

Interacts with 178 drugs

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control in certain people with type 2 diabetes, b...

Read the full Chromium monograph → Herb & supplement monograph

Molybdenum

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so supplements are rarely needed unless a do...

Read the full Molybdenum monograph → Herb & supplement monograph

Vitamin A

Interacts with 387 drugs

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplements are mainly useful for correcting a tr...

Read the full Vitamin A monograph → Herb & supplement monograph

Riboflavin

Interacts with 20 drugs

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally very safe at typical doses, and the stro...

Read the full Riboflavin monograph → Herb & supplement monograph

Coenzyme Q10

Interacts with 198 drugs

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated and is most studied for heart condition...

Read the full Coenzyme Q10 monograph →
Sources

Sources & How We Checked

Cir-Q Tonic's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 557 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Thiamine 7 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  4. Rogovik, A. L., Vohra, S., and Goldman, R. D. Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? Ann.Pharmacother. 2010;44(2):311-324. PubMed
  5. Arruti N, Bernedo N, Audicana MT, Villarreal O, Uriel O, Muñoz D. Systemic allergic dermatitis caused by thiamine after iontophoresis. Contact Dermatitis. 2013 Dec;69(6):375-6. PubMed
  6. Thiamine hydrochloride injection package insert. Lake Zurich, IL: Fresenius Kabi, LLC; September 2019.
  7. Vora B, Wen A, Yee SW, et al. The Effect of Trimethoprim on Thiamine Absorption: A Transporter-Mediated Drug-Nutrient Interaction. Clin Pharmacol Ther 2023;114(2):381-392.

See these in context on the Thiamine monograph →

Biotin 4 references
  1. Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  3. Mock DM, Quirk JG, Mock NI. Marginal biotin deficiency during normal pregnancy. Am J Clin Nutr 2002;75:295-9. PubMed
  4. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.Mult Scler Relat Disord. 2015;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. PubMed

See these in context on the Biotin monograph →

Pantothenic Acid 11 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
  4. Schmuth, M., Wimmer, M. A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D. M., Elias, P. M., Fritsch, P. O., and Fritsch, E. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study. Br.J.Dermatol. 2 PubMed
  5. Schreck, U., Paulsen, F., Bamberg, M., and Budach, W. Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder? Strahlenther.Onkol. 2002;178(6):321-329. PubMed
  6. Herbst, R. A., Uter, W., Pirker, C., Geier, J., and Frosch, P. J. Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period. Contact Dermatitis 2004;51(1):13-1 PubMed
  7. Champault, G. and Patel, J. C. [Treatment of constipation with Bepanthene]. Med.Chir Dig. 1977;6(1):57-59.
  8. Scott LN, Fiume M, Bergfeld WF, et al. Safety Assessment of Panthenol, Pantothenic Acid, and Derivatives as Used in Cosmetics. Int J Toxicol 2022;41(3_suppl):77-128. PubMed
  9. Han J, Warshaw EM. Allergic Contact Dermatitis to Panthenol in "Hypoallergenic" Products. Dermatitis 2023;34(1):62-63. PubMed
  10. Blanchard G, Kerre S, Walker A, et al. Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams. Contact Dermatitis 2022;87(5):468-471. PubMed
  11. Peltier E, Trapp S, de Salvo R, et al. A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function. J Cosme PubMed

See these in context on the Pantothenic Acid monograph →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D monograph →

Iron 72 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non- anaemic iron-deficient adolescent girls. Lancet 1996;348:992-6.
  3. Ullen H, Augustsson K, Gustavsson C, Steineck G. Supplementary iron intake and risk of cancer: reversed causality? Cancer Lett 1997;114:215-6.
  4. Reunanen A, Takkunen H, Knekt P, et al. Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 1995;238:223-30. PubMed
  5. Lund EK, Wharf SG, Fairweather-Tait SJ, Johnson IT. Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. Am J Clin Nutr 1999;69:250-5.
  6. Rehman A, Collis CS, Yang M, et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Comm 1998;246:293-8. PubMed
  7. Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, et al. Dietary iron and risk of myocardial infarction in the Rotterdam Study. Am J Epidemiol 1999;149:421-8. PubMed
  8. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  9. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Campbell N, Paddock V, Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther 1988;43:381-6..
  12. Schumann K, Borch-Iohnsen B, Hentze MW, Marx JJ. Tolerable upper intakes for dietary iron set by the US Food and Nutrition Board (commentary). Am J Clin Nutr 2002;76:499-500. PubMed
  13. Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 1998;97:1461-6.. PubMed
  14. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992;86:803-11.. PubMed
  15. Campbell NRC, Hasinoff B. Ferrous sulfate reduces levodopa bioavailability: Chelation as a possible mechanism. Clin Pharmacol Ther 1989;45:220-5.. PubMed
  16. Campbell NRC, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Int Med 1992;117:1010-3.. PubMed
  17. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 1997;96:3300-07. PubMed
  18. Comparison of oral iron supplements. Pharmacist's Letter / Prescriber's Letter 2008;24(8):240811.
  19. Tran T., Wax J. R., Philput C., Steinfeld J. D., Ingardia C. J. Intentional iron overdose in pregnancy--management and outcome. J Emerg Med 2000;18(2):225-228. PubMed
  20. Toblli J. E., Brignoli, R. Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis. Arzneimittelforschung 2007;57(6A):431-438. PubMed
  21. Köpcke W., Sauerland M. C. Meta-analysis of efficacy and tolerability data on iron proteinsuccinylate in patients with iron deficiency anemia of different severity. Arzneimittelforschung 1995;45(11):1211-1216.
  22. Campbell N. R., Campbell R. R., Hasinoff B. B. Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism. Clin Invest Med 1990;13(6):329-332.
  23. Morii M., Ueno K., Ogawa A., Kato R., Yoshimura H., Wada K., Hashimoto H., Takada M., Tanaka K., Nakatani T., Shibakawa M. Impairment of mycophenolate mofetil absorption by iron ion. Clin Pharmacol Ther 2000;68(6):613-616. PubMed
  24. Gelone D. K., Park J. M., Lake K. D. Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients. Pharmacotherapy 2007;27(9):1272-1278. PubMed
  25. Ducray P. S., Banken L., Gerber M., Boutouyrie B., Zandt H. Absence of an interaction between iron and mycophenolate mofetil absorption. Br J Clin Pharmacol 2006;62(4):492-495. PubMed
  26. Lorenz M., Wolzt M., Weigel G., Puttinger H., Hörl W. H., Födinger M., Speiser W., Sunder-Plassmann G. Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients. Am J Kidney Dis 2004;43(6):1098-1103. PubMed
  27. Osman M. A., Patel R. B., Schuna A., Sundstrom W. R., Welling P. G. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther 1983;33(4):465-470. PubMed
  28. Michael, B., Coyne, D. W., Fishbane, S., Folkert, V., Lynn, R., Nissenson, A. R., Agarwal, R., Eschbach, J. W., Fadem, S. Z., Trout, J. R., Strobos, J., and Warnock, D. G. Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compar
  29. Zhang, X., Ouyang, J., Wieczorek, R., and DeSoto, F. Iron medication-induced gastric mucosal injury. Pathol.Res Pract 2009;205(8):579-581. PubMed
  30. Barbieri, P. G. [To-day exposure to occupational carcinogens and their effects. The experience of the rubber industry, iron metallurgy, asphalt work and aviculture]. Epidemiol.Prev 2009;33(4-5 Suppl 2):94-105.
  31. Macedo, A. and Cardoso, S. [Routine iron supplementation in pregnancy]. Acta Med Port. 2010;23(5):785-792.
  32. Bastide, N. M., Pierre, F. H., and Corpet, D. E. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res (Phila) 2011;4(2):177-184. PubMed
  33. Stevens, R. G. Iron and the risk of cancer. Med Oncol Tumor Pharmacother. 1990;7(2-3):177-181. PubMed
  34. van den, Hombergh J., Dalderop, E., and Smit, Y. Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania. J.Trop.Pediatr. PubMed
  35. Liabeuf S, Gras V, Moragny J, et al. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database. Clin Interv Aging. 2014 Apr 25;9:737-40. PubMed
  36. Qiao L, Feng Y. Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies. Cancer Causes Control. 2013 Jun;24(6):1175-83. PubMed
  37. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  38. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescen
  39. Song I, Borland J, Arya N, Wynne B, Piscitelli S. Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. J Clin Pharmacol. 2015;55(5):490-6. PubMed
  40. Esan MO, Boele van Hensbroek M, Nkhoma E, et al. Iron supplementation in HIV infected Malawian children with anemia: a double-blind, randomized, controlled trial. Clin Inf Dis 2013;57(11):1626-34.doi:10.1093/cid/cit528. PubMed
  41. Zlotkin S, Newton S, Aimone AM, et al. Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial. JAMA 2013;310(9):938-47. PubMed
  42. Khambalia AZ, Aimone A, Nagubandi P, et al. High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. Diabet Med. 2016;33(9):1211-21. PubMed
  43. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016;12(1):74-84.
  44. Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;4:CD009747. PubMed
  45. Melit LE, Marginean CO, Mocanu S, Marginean MO. A rare case of iron-pill induced gastritis in a female teenager: A case report and a review of the literature. Medicine (Baltimore). 2017;96(30):e7550. PubMed
  46. Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016;2:CD006589. PubMed
  47. Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-Urrutia MC, Dowswell T. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(10):CD009997. PubMed
  48. Brabin B, Gies S, Roberts SA, et al. Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso. Mala PubMed
  49. Kaundal R, Bhatia P, Jain A, et al. Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia. Ann Hematol 2020;99(1):57-63. PubMed
  50. Li N, Zhao G, Wu W, et al. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: A randomized clinical trial. JAMA Netw Open. 2020;3(11):e2023644.<br> PubMed
  51. Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018;8(4):e019240. PubMed
  52. Koch RM, Tchernodrinski S, Principe DR. Case report: Rapid onset, ischemic-type gastritis after initiating oral iron supplementation. Front Med (Lausanne) 2022;9:1010897. PubMed
  53. Milman NT. Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled
  54. Rogozinska E, Daru J, Nicolaides M, et al. Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis. Lancet Haematol 2021;8(7):e503-e512. PubMed
  55. Shah AA, Donovan K, Seeley C, et al. Risk of infection associated with administration of intravenous iron: A systematic review and meta-analysis. JAMA Netw Open 2021;4(11):e2133935. PubMed
  56. Gamad N, Saha PK, Sharma P, Suri V, Chakrabarti A, Saha L. A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy. J Obstet Gynaecol Res 2021;47(11):3828-3841. PubMed
  57. El-Hawy MA, Abd Al-Salam SA, Bahbah WA. Comparing oral iron bisglycinate chelate, lactoferrin, lactoferrin with iron and iron polymaltose complex in the treatment of children with iron deficiency anemia. Clin Nutr ESPEN 2021;46:367-371. PubMed
  58. Adams A, Scheckel B, Habsaoui A, et al. Intravenous iron versus oral iron versus no iron with or without erythropoiesis- stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis. Cochrane Database Syst Rev 2 PubMed
  59. Kancherla K, Constantin H, Kanawati A, Graham E. Iron-induced Hypophosphatemic Osteomalacia-An Atypical Case of Bilateral Femoral Stress Fractures. J Am Acad Orthop Surg Glob Res Rev 2023;7(5):e22. PubMed
  60. Shi R, Marin JG, Beaulieu M. Skin staining following intravenous iron extravasation in a patient with chronic kidney disease: A case report. Can J Kidney Health Dis 2023;10:20543581231165705. PubMed
  61. Varandas C, Vieira J, Correia CJ, et al. Hypersensitivity reactions to iron products: 10-year experience in a Portuguese tertiary Centre. Eur Ann Allergy Clin Immunol 2023.
  62. Jara Vidal M, López García MC, Quílez Toboso RP. Kounis syndrome after intravenous iron administration. Med Clin (Barc) 2023. DOI
  63. Jara Vidal M, Ruiz de Assín Valverde A, Aznar Rodríguez S. Severe hypophospathemia secondary to intravenous iron. Med Clin (Barc) 2023. DOI
  64. Samões B, Silva B, Martins A, et al. Hypophosphatemic osteomalacia induced by intravenous iron therapy: a case report. Joint Bone Spine 2023;90(5):105586. PubMed
  65. Seng NW, Barco JB, Wong MH, et al. Hypophosphatemia related to intravenous iron therapy with ferric carboxymaltose: A case series. Transfus Med 2023. PubMed
  66. Fernandez-Flores A, Fernandez-Parrado M, Alzoghby-Abi Chaker J, Angulo AG. Axillary cutaneous hemosiderosis in a patient with hyperhidrosis, after intravenous iron infusion. Am J Dermatopathol 2023;45(7):463-465. PubMed
  67. Ye S, Grill V, Luo J, Nguyen HH. Concurrent Denosumab and Parenteral Iron Therapy Precipitating Severe Hypocalcemia and Hypophosphatemia. JCEM Case Rep 2024;2(2):luae005. PubMed
  68. Yerigeri K. Hemochromatosis in an Adult Female With Previous Iron Deficiency Anemia on Iron Supplementation. Cureus 2023;15(12):e50166. PubMed
  69. Meyers M, Salmon M, Libert I, Klá&scaron;terský J. A meta-analysis on the risk of infection associated with intravenous iron therapy in cancer-associated anaemia: a double-edged sword?. Curr Opin Oncol 2024;36(4):223-232. PubMed
  70. Short V, Allen R, Earley CJ, et al. A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia. Am J Hem PubMed
  71. Bellos I, Frountzas M, Pergialiotis V. Comparative Risk of Hypophosphatemia Following the Administration of Intravenous Iron Formulations: A Network Meta-Analysis. Transfus Med Rev 2020;34(3):188-194. PubMed
  72. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Iron monograph →

Vitamin B12 30 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  2. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. DOI
  3. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  4. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  5. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  6. Geissbuhler, P., Mermillod, B., and Rapin, C. H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: a prospective study over five years. J.Pain Symptom.Manage. 2000;20(2):93-103. PubMed
  7. Salles, N., Herrmann, F., Sakbani, K., Rapin, C. H., and Sieber, C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr.Soc 2005;53(5):917-918.
  8. Looker, H. C., Fagot-Campagna, A., Gunter, E. W., Pfeiffer, C. M., Sievers, M. L., Bennett, P. H., Nelson, R. G., Hanson, R. L., and Knowler, W. C. Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res R
  9. Uhl, W., Nolting, A., Golor, G., Rost, K. L., and Kovar, A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila) 2006;44 Suppl 1:17-28. PubMed
  10. Borron, S. W., Baud, F. J., Barriot, P., Imbert, M., and Bismuth, C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg.Med 2007;49(6):794-801, 801. PubMed
  11. Borron, S. W., Baud, F. J., Megarbane, B., and Bismuth, C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg.Med 2007;25(5):551-558. PubMed
  12. Lewis, J. G. Gout, Steatorrhoea, and Megaloblastic Anaemia. Ann Rheum.Dis 1962;21(3):284-286. PubMed
  13. Tal, S., Shavit, Y., Stern, F., and Malnick, S. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr.Soc 2010;58(3):523-526. PubMed
  14. Baztan, J. J., Gavidia, J. J., Gomez-Pavon, J., Esteve, A., and Ruiperez, I. High vitamin B12 levels and in-hospital mortality. J Am Geriatr.Soc 2010;58(11):2237-2238. PubMed
  15. Omboni, E., Checchini, M., and Longoni, F. [Hypopotassemia and megaloblastic anemia. Presentation of a case]. Minerva Med 8-31-1987;78(16):1255-1257.
  16. Aalfs As, Scholvinck LH, Horvath B. Acneiform eruption in a 5-year old due to vitamin B12 supplementation. Eur J Dermatol 2013;23(5):726-7. PubMed
  17. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan Ocul Toxicol 2014;33(2):94-5. PubMed
  18. Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emerg Care 2013;29(11):1223-4. PubMed
  19. Djuric V, Bogic M, Popadic AP, et al. Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin. Ann Allergy Asthma Immunol 2012;108(3):207-8. PubMed
  20. Kartel O, Gulec M, Demirel F, et al. Vitamin B12 allergy and successful desensitization with cyanocobalamin: A case report. Allergol Immunopath (Madr) 2012;40(5):324-5.
  21. Patiroglu T, Unal E, Yildirim S. Infantile tremor syndrome associated with cobalamin therapy: A case report. Clin Neurol Neurosurg 2013;115(9):1903-5. PubMed
  22. Schulte S, Barkema LW, Kardaun SH. Long-lasting atypical acneiform eruption with prominent comedones induced by hydroxocobalamin (vitamin B12). J Dtsch Dermatol Ges 2014;12(6):502-3.
  23. Zanus C, Alberini E, Costa P, et al. Involuntary movements after correction of vitamin B12 deficiency: A video-case report. Epileptic Disord 2012;14(2):174-80. PubMed
  24. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  25. Fujita Y, Mizukami T, Maya Y, et al. Vitamin B12 allergy manifesting as lymphomatoid contact dermatitis. Eur J Dermatol. 2020;30(3):304-305. PubMed
  26. Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Crit Care. 2019;23(1):421. PubMed
  27. Khairan P, Sobue T, Eshak ES, et al. Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study. BMC Cancer 2021;21(1):982. PubMed
  28. Evans J, Pandya A, Ding Y, Qunibi WY. Hydroxocobalamin-Induced Oxalate Nephropathy in a Patient With Smoke Inhalation. Kidney Int Rep 2021;6(8):2228-2231. PubMed
  29. Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Sci Rep 2021;11(1):13361. PubMed
  30. Pegalajar-García MD, Cebolla-Verdugo M, Prados-Carmona Á, Llamas-Segura C, Navarro-Triviño FJ. Systemic allergic dermatitis to cobalt present in cyanocobalamin supplementation. Contact Dermatitis 2023;89(3):203-205. PubMed

See these in context on the Vitamin B12 monograph →

Selenium 36 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  2. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  3. Trafikowska U, Zachara BA, Wiacek M, et al. Selenium supply and glutathione peroxidase activity in breastfed Polish infants. Acta Paediatr 1996;85:1143-5. PubMed
  4. Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 2003;95:1477-81.. PubMed
  5. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  6. Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96. PubMed
  7. Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83. DOI
  8. Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.
  9. Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7. PubMed
  10. Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32. PubMed
  11. Contempre B, Dumont JE, Ngo B, et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol PubMed
  12. Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997;73:103-4. PubMed
  13. Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53. PubMed
  14. Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85. PubMed
  15. Lippmann SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51. DOI
  16. Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752. PubMed
  17. Vinceti, M., Wei, E. T., Malagoli, C., Bergomi, M., and Vivoli, G. Adverse health effects of selenium in humans. Rev.Environ.Health 2001;16(4):233-251. PubMed
  18. Abrams, C. K., Siram, S. M., Galsim, C., Johnson-Hamilton, H., Munford, F. L., and Mezghebe, H. Selenium deficiency in long-term total parenteral nutrition. Nutr Clin Pract 1992;7(4):175-178. PubMed
  19. Spiller, H. A. and Pfiefer, E. Two fatal cases of selenium toxicity. Forensic Sci Int 8-24-2007;171(1):67-72. PubMed
  20. Negro, R., Greco, G., Mangieri, T., Pezzarossa, A., Dazzi, D., and Hassan, H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol.Metab 2007;92(4):1263-1268. PubMed
  21. Alexander, J. Selenium. Novartis.Found.Symp 2007;282:143-149.
  22. Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial
  23. Kupka, R., Mugusi, F., Aboud, S., Msamanga, G. I., Finkelstein, J. L., Spiegelman, D., and Fawzi, W. W. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and chil
  24. Kamble, P., Mohsin, N., Jha, A., Date, A., Upadhaya, A., Mohammad, E., Khalil, M., Pakkyara, A., and Budruddin, M. Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis. Saudi.J Kidney Dis.Transpl. 2009;20(1):106
  25. Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328. PubMed
  26. Kumpulainen, J., Salmenpera, L., Siimes, M. A., Koivistoinen, P., and Perheentupa, J. Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation. Am.J Clin.Nutr. 1985;42(5):829-835. PubMed
  27. Han, L. and Zhou, S. M. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl) 1994;107(11):870-871.
  28. Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127. PubMed
  29. Srivastava, A. K., Gupta, B. N., Bihari, V., and Gaur, J. S. Generalized hair loss and selenium exposure. Vet.Hum.Toxicol. 1995;37(5):468-469.
  30. Sudfeld CR, Aboud S, Kupka R, et al. Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women. Nutrition 2014;30(9):1081-4. PubMed
  31. Rees K, Hartley L, Day C, et al. Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD009671. PubMed
  32. Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. J Natl Cancer Inst. 2016;108(12). PubMed
  33. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 2016;26(12):1681-92. PubMed
  34. Vinceti M, Filippini T, Rothman KJ. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol. 2018 Sep;33(9):789-810. Epub 2018 Jul 5. Review. PubMed
  35. Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3. PubMed
  36. Malpas CB, Vivash L, Genc S, et al. A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease. J Alzheimers Dis. 2016;54(1):223-232. PubMed

See these in context on the Selenium monograph →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C monograph →

Vanadium 15 references
  1. Harland BF, Harden-Williams BA. Is vanadium of human nutritional importance yet? J Am Diet Assoc 1994;94:891-4. PubMed
  2. Sitprija V, Tungsanga K, Tosukhowong P, et al. Metabolic problems in northeastern Thailand: possible role of vanadium. Mineral Electrolyte Metab 1998;19:51-6.
  3. Funakoshi T, Shimada H, Kojima S, et al. Anticoagulant action of vanadate. Chem Pharmaceut Bull 1992;40:174-6. PubMed
  4. Halberstam M, Cohen N, Shlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes 1996;45:659-66. PubMed
  5. Cohen N, Halberstam M, Shlimovich P, et al. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1995;95:2501-9. PubMed
  6. Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 1996;45:1130-5.
  7. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  8. Goldfine AB, Simonson DC, Folli F, et al. Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies. J Clin Endocrinol Metab 1995;80:3311-20. PubMed
  9. Cusi K, Cukier S, DeFronzo RA, et al. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab 2001;86:1410-7.
  10. Peat F, Coomber R, Rana A, Vince A. Vanadium allergy following total knee arthroplasty. BMJ Case Rep 2018;2018. pii: bcr-2017-222092. doi: 10.1136/bcr-2017-222092. PubMed
  11. Jin S, Xia W, Jiang Y, et al. Urinary vanadium concentration in relation to premature rupture of membranes: A birth cohort study. Chemosphere 2018;210:1035-41. doi: 10.1016/j.chemosphere.2018.07.110. PubMed
  12. Garcia-Nunez I, Algaba-Marmol MA, Suarez-Vergara M, et al. Vanadium contact dermatitis: case report and studies performed. Contact Dermatitis 2019;80(2):127-8. PubMed
  13. Zhou Y, Zhu Q, Ma W, et al. Prenatal vanadium exposure, cytokine expression, and fetal growth: a gender-specific analysis in Shanghai MCPC study. Sci Total Environ 2019;685:1152-9. PubMed
  14. Jiang S, Zhou S, Liu H, et al. Concentrations of vanadium in urine with hypertension prevalence and blood pressure levels. Ecotoxicol Environ Saf 2021;213:112028. PubMed
  15. Zhang W, Chen H, Zeng Q, Xu S, Xia W, Li Y. Prenatal and postnatal exposure to vanadium and the immune function of children. J Trace Elem Med Biol 2021;67:126787. PubMed

See these in context on the Vanadium monograph →

Manganese 21 references
  1. Hansten PD, Horn JR. Hansten and Horn's Drug Interactions Analysis and Management. Vancouver, CAN:Appl Therapeut, 1999.
  2. Barrington WW, Angle CR, Willcockson NK, et al. Autonomic function in manganese alloy workers. Environ Res 1998;78:50-8. PubMed
  3. Hauser RA, Zesiewicz TA, Martinez C, et al. Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can J Neurol Sci 1996;23:95-8. PubMed
  4. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  5. Lee JW. Manganese intoxication. Arch Neurol 2000;57:597-9.. PubMed
  6. Powers KM, Smith-Weller T, Franklin GM, et al. Parkinson's disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology 2003;60:1761-6.. PubMed
  7. McMillan, D. E. A brief history of the neurobehavioral toxicity of manganese: some unanswered questions. Neurotoxicology 1999;20(2-3):499-507.
  8. Gerber, G. B., Leonard, A., and Hantson, P. Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. Crit Rev Oncol Hematol. 2002;42(1):25-34. PubMed
  9. Jiang, Y. and Zheng, W. Cardiovascular toxicities upon manganese exposure. Cardiovasc.Toxicol 2005;5(4):345-354. PubMed
  10. Mehta, R. and Reilly, J. J. Manganese levels in a jaundiced long-term total parenteral nutrition patient: potentiation of haloperidol toxicity? Case report and literature review. JPEN J Parenter.Enteral Nutr 1990;14(4):428-430. PubMed
  11. Nemery, B. Metal toxicity and the respiratory tract. Eur Respir.J 1990;3(2):202-219. DOI
  12. Vanek VW, Borum P, Buchman A, et al. A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products. Nutr Clin Pract. 2012;27:440-491.doi: 10.1177/0884533612446706 PubMed
  13. Schuh MJ. Possible Parkinson's disease induced by chronic manganese supplement ingestion. Consult Pharm. 2016;31(12):698-703. doi: 10.4140/TCP.n.2016.698. PubMed
  14. Baker B, Ali A, Isenring L. Recommendations for manganese supplementation to adult patients receiving long-term home parenteral nutrition: an analysis of the supporting evidence. Nutr Clin Pract 2016;31(2):180-5. doi: 10.1177/0884533615591600. PubMed
  15. Ho CSH, Ho RCM, Quek AML. Chronic manganese toxicity associated with voltage-gated potassium channel complex antibodies in a relapsing neuropsychiatric disorder. Int J Environ Res Public Health 2018;15(4). pii: E783. doi: 10.3390/ijerph15040783. PubMed
  16. Yamamoto M, Sakurai K, Eguchi A, et al.; Japan Environment and Children's Study Group: Association between blood manganese level during pregnancy and birth size: the Japan environment and children's study (JECS). Environ Res 2019;172:117-26. PubMed
  17. Li D, Ge X, Liu Z, et al. Association between long-term occupational manganese exposure and bone quality among retired workers. Environ Sci Pollut Res Int 2020;27(1):482-9. PubMed
  18. Martin KV, Sucharew H, Dietrich KN, et al. Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio. Environ Res 2021;202:111644. PubMed
  19. Racette BA, Nelson G, Dlamini WW, et al. Depression and anxiety in a manganese-exposed community. Neurotoxicology 2021;85:222-33. PubMed
  20. Ruiz-Azcona L, Fernández-Olmo I, Expósito A, et al. Impact of environmental airborne manganese exposure on cognitive and motor functions in adults: a systematic review and meta-analysis. Int J Environ Res Public Health 2021;18(8):4075. PubMed
  21. Uyar E, Gurkas E, Aksu AU, et al. Can therapeutic plasma exchange be life-saving in life-threatening manganese intoxication?. Transfus Apher Sci 2022;61(4):103417. PubMed

See these in context on the Manganese monograph →

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Chromium 53 references
  1. Cerulli J, Grabe DW, Gauthier I, et al. Chromium picolinate toxicity. Ann Pharmacother 1998;32:428-31. PubMed
  2. Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:896-9. PubMed
  3. Mohamedshah FY, Moser-Veillon PB, Yamini S, et al. Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast milk in lactating women. Am J Clin Nutr 1998;67:1250-5. PubMed
  4. Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. [letter]. Ann Intern Med 1997;126:410. PubMed
  5. Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998;56:174-7. PubMed
  6. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998;17:548-55. PubMed
  7. McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psych 1999;60:237-40. PubMed
  8. Fowler JF Jr. Systemic contact dermatitis caused by oral chromium picolinate. Cutis 2000;65:116. DOI
  9. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35:273-80.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82. PubMed
  12. Lanca S, Alves A, Vieira AI, et al. Chromium-induced toxic hepatitis. Eur J Intern Med 2002;13:518-20. PubMed
  13. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  14. Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-4.. PubMed
  15. Food Standards Agency. Medicines and Healthcare products Regulatory Agency (MHRA). Expert Group on Vitamins and Minerals. Available at: http://cot.food.gov.uk/sites/default/files/vitmin2003.pdf.
  16. Mouser JF, Hak EB, Helms RA, et al. Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition. Am J Health Syst Pharm 1999;56:1950-6. PubMed
  17. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005;142:477-8. PubMed
  18. Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. Ann Pharmacother 2006;40:563-6. PubMed
  19. Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2006;29: PubMed
  20. Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. PubMed
  21. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006;8:636-43. PubMed
  22. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007;17:763-5. PubMed
  23. Yazaki Y, Faridi Z, Ma Y, et al. A pilot study of chromium picolinate for weight loss. J Altern Complement Med 2010;16:291-9. PubMed
  24. Davis ML, Seaborn CD, and Stoecker BJ. Effects of over-the-counter drugs on chromium retention and urinary excretion in rats. Nutrition Research 1995;15(2):201-210.
  25. Young P, Turiansky G, Bonner M, and et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J.Am Acad.Dermatol. 1999;41(5 Pt 2):820-823. PubMed
  26. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Lung cancer among workers in chromium chemical production. Am J Ind.Med 2000;38(2):115-126. DOI
  27. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Clinical findings of irritation among chromium chemical production workers. Am J Ind.Med 2000;38(2):127-131. PubMed
  28. Pittler, M. H. and Ernst, E. Dietary supplements for body-weight reduction: a systematic review. Am.J.Clin Nutr. 2004;79(4):529-536. PubMed
  29. Pei, D., Hsieh, C. H., Hung, Y. J., Li, J. C., Lee, C. H., and Kuo, S. W. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 2 PubMed
  30. Hisatomi, K., Ishii, H., Hashiguchi, K., Seki, M., Ide, M., Sugiyama, K., Ishimoto, H., Nakayama, S., Mukae, H., and Kohno, S. Interstitial pneumonia caused by inhalation of fumes of nickel and chrome. Respirology. 2006;11(6):814-817. PubMed
  31. Kleefstra, N., Houweling, S. T., Bakker, S. J., Verhoeven, S., Gans, R. O., Meyboom-de Jong, B., and Bilo, H. J. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled tri DOI
  32. Parsons, A., Ingram, J., Inglis, J., Aveyard, P., Johnstone, E., Brown, K., Franklin, M., and Bermudez, I. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to pr
  33. Bagdon RE and Hazen RE. Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant. Environ.Health Perspect. 1991;92:111-119. PubMed
  34. Bharmal, S. V., Moyes, V., Ahmed, S., and Grossman, A. Hypoglycaemia: possible mediation by chromium salt medication. Hormones.(Athens.) 2010;9(2):181-183. PubMed
  35. Krol, E., Krejpcio, Z., Byks, H., Bogdanski, P., and Pupek-Musialik, D. Effects of chromium brewer's yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol.Trace Elem.Res. 2011;143(2):726-737.
  36. Unisa, S., Jagannath, P., Dhir, V., Khandelwal, C., Sarangi, L., and Roy, T. K. Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB (Oxford) 2011;13(2):117-125. PubMed
  37. Noda, S., Asano, Y., and Sato, S. Lichen planus in a patient with long-term exposure to chrome. Eur.J.Dermatol. 2011;21(3):417-418. PubMed
  38. Xiang, J., Sun, Z., and Huan, J. N. Intensive chromic acid burns and acute chromium poisoning with acute renal failure. Chin Med.J.(Engl.) 7-5-2011;124(13):2071-2073.
  39. Chhabra, D., Oda, K., Jagannath, P., Utsunomiya, H., Takekoshi, S., and Nimura, Y. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac.J.Cancer Prev. 2012;13(1):187-190. PubMed
  40. Huszonek, J. Over-the-counter chromium picolinate. Am J Psychiatry 1993;150(10):1560-1561. PubMed
  41. Bunner S and McGinnis R. Chromium-induced hypoglycemia. Psychosomatics 1998;39(3):298-299. PubMed
  42. Martin, W. R. and Fuller, R. E. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy 1998;18(4):860-862. DOI
  43. Proctor, D. M., Fredrick, M. M., Scott, P. K., Paustenbach, D. J., and Finley, B. L. The prevalence of chromium allergy in the United States and its implications for setting soil cleanup: a cost-effectiveness case study. Regul.Toxicol Pharmacol 1998;28(1 PubMed
  44. De Marchi S, Cecchin E, De Marchi SU. Systemic allergic dermatitis resulting from oral administration of chromium with a food supplement. Contact Dermatitis 2014;70(2):123-5. PubMed
  45. Hedberg YS, Gumulka M, Lind ML, Matura M, Lidén C. Severe occupational chromium allergy despite cement legislation. Contact Dermatitis. 2014;70(5):321-3. PubMed
  46. Thyssen JP, Jellesen MS, Møller P, Menné T, Johansen JD. Allergic chromium dermatitis from wearing 'chromium-free' footwear. Contact Dermatitis 2014;70(3):185-7. PubMed
  47. Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One.
  48. Jamilian M, Asemi Z. Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2015;67(1):42-8. PubMed
  49. Guimarães MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. J Trace Elem Med Bi PubMed
  50. Paiva AN, Lima JG, Medeiros AC, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015;32:66-72. PubMed
  51. Yin RV, Phung OJ. Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus. Nutr J. 2015;14:14. PubMed
  52. Jamilian M, Zadeh Modarres S, Amiri Siavashani M, et al. The influences of chromium supplementation on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilizati
  53. Alinaghi F, Thyssen JP, Zachariae C, Johansen JD. No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy. Contact Dermatitis 2021;85(5):514-522. PubMed

See these in context on the Chromium monograph →

Molybdenum 8 references
  1. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  3. Rajagopalan KV. Molybdenum: an essential trace element in human nutrition. Annu Rev Nutr 1988;8:401-27. PubMed
  4. Selden AI, Berg NP, Soderbergh A, Bergstrom BE. Occupational molybdenum exposure and a gouty electrician. Occup Med (Lond) 2005;55:145-8. PubMed
  5. Al-Saleh E, Nandakumaran M, Al-Shammari M, Al-Harouny A. Maternal-fetal status of copper, iron, molybdenum, selenium and zinc in patients with gestational diabetes. J Matern Fetal Neonatal Med 2004;16:15-21. PubMed
  6. Koster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet 2000;356:1895-7. PubMed
  7. Vyskocil A, Viau C. Assessment of molybdenum toxicity in humans. J Appl Toxicol 1999;19:185-92. DOI
  8. Momcilovic, B. A case report of acute human molybdenum toxicity from a dietary molybdenum supplement--a new member of the "Lucor metallicum" family. Arh.Hig.Rada Toksikol. 1999;50(3):289-297. DOI

See these in context on the Molybdenum monograph →

Vitamin A 31 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Griffiths JK. The vitamin A paradox. J Pediatr 2000;137:604-7.. PubMed
  3. Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. FDA Talk Paper. Vitamin A and birth defects (T95-56). Food and Drug Administration, U.S. Department of Health and Human Services, Rockville, MD. October 6, 1995.
  6. Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr 2000;71:878-84. PubMed
  7. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  8. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47-54. PubMed
  9. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-8. PubMed
  10. Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348:287-94.. PubMed
  11. Botterweck AA, van den Brandt PA, Goldbohm RA. Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up. Cancer 2000;88:737-48.. DOI
  12. Meyskens FL Jr, Graham V, Chvapil M, et al. A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia. J Natl Cancer Inst 1983;71:921-5..
  13. Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52:183-202.. PubMed
  14. Walters BN, Gubbay SS. Tetracycline and benign intracranial hypertension: report of five cases. Br Med J 1981;282:19-20.. PubMed
  15. Pearson MG, Littlewood SM, Bowden AN. Tetracycline and benign intracranial hypertension (letter). Br Med J 1981;282:568-9.. PubMed
  16. Azais-Braesco V, Pascal G. Vitamin A in pregnancy: requirements and safety limits. Am J Clin Nutr 2000;71:1325S-33S. PubMed
  17. Smedts HP, de Vries JH, Rakhshandehroo M, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG 2009;116:416-23. PubMed
  18. Grotto, I., Mimouni, M., Gdalevich, M., and Mimouni, D. Vitamin A supplementation and childhood morbidity from diarrhea and respiratory infections: a meta-analysis. J Pediatr 2003;142(3):297-304. PubMed
  19. Mahalanabis, D., Lahiri, M., Paul, D., Gupta, S., Gupta, A., Wahed, M. A., and Khaled, M. A. Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute l
  20. Long, K. Z., Montoya, Y., Hertzmark, E., Santos, J. I., and Rosado, J. L. A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mex
  21. Fritz, H., Kennedy, D., Fergusson, D., Fernandes, R., Doucette, S., Cooley, K., Seely, A., Sagar, S., Wong, R., and Seely, D. Vitamin A and retinoid derivatives for lung cancer: a systematic review and meta analysis. PLoS.One. 2011;6(6):e21107. PubMed
  22. Mayo-Wilson, E., Imdad, A., Herzer, K., Yakoob, M. Y., and Bhutta, Z. A. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ 2011;343:d5094. PubMed
  23. Mazumder S, Taneja S, Bhatia K, Yoshida S, Kaur J, Dube B, Toteja GS, Bahl R, Fontaine O, Martines J, Bhandari N; Neovita India Study Group. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovit
  24. Baineni R, Gulati R, Delhi CK. Vitamin A toxicity presenting as bone pain. Arch Dis Child. 2017;102(6):556-8. PubMed
  25. Darlow BA, Graham PJ, Rojas-Reyes MX. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016;(8):CD000501. PubMed
  26. Haider BA, Sharma R, Bhutta ZA. Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in low and middle income countries. Cochrane Database Syst Rev. 2017;2:CD006980. PubMed
  27. Mohammad YM, Raslan IR, Al-Hussain FA. Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A. J Neuroophthalmol. 2016;36(4):412-3. PubMed
  28. Masnadi Shirazi K, Nikniaz Z, Masnadi Shirazi A, Rohani M. Vitamin A supplementation decreases disease activity index in patients with ulcerative colitis: A randomized controlled clinical trial. Complement Ther Med. 2018 Dec;41:215-219. PubMed
  29. Ding Y, Hu P, Yang Y, et al. Impact of maternal daily oral low-dose vitamin A supplementation on the mother-infant pair: a randomised placebo-controlled trial in China. Nutrients 2021;13(7):2370. PubMed
  30. Knapik JJ, Hoedebecke SS. Vitamin A and bone fractures: systematic review and meta-analysis. J Spec Oper Med 2021;21(2):100-7. PubMed
  31. Imdad A, Mayo-Wilson E, Haykal MR, et al. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev 2022;3(3):CD008524. PubMed

See these in context on the Vitamin A monograph →

Riboflavin 5 references
  1. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70. PubMed
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7. PubMed
  4. MacLennan, S. C., Wade, F. M., Forrest, K. M., Ratanayake, P. D., Fagan, E., and Antony, J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol. 2008;23(11):1300-1304.
  5. Dietary reference intakes (DRIs): estimated average requirements. Food and Nutrition Board, Institute of Medicine, National Academics. https://www.nal.usda.gov/sites/default/files/fnic_uploads//recommended_intakes_individuals.pdf Accessed July 24, 2017.

See these in context on the Riboflavin monograph →

Coenzyme Q10 40 references
  1. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol 1985;56:247-51. PubMed
  2. Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994;S265-72. PubMed
  3. Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;334:1372-3. PubMed
  4. Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-8. PubMed
  5. Portakal O, Ozkaya O, Erden Inal M, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-84. PubMed
  6. Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-6. PubMed
  7. Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol 1990;65:521-3. PubMed
  8. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  9. Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-7.
  10. Baggio E, Gandini R, Plauncher AC, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994;15 Suppl:S287-94. PubMed
  11. Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001;94:1112-7. PubMed
  12. The Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001;57:397-404.
  13. Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-42. PubMed
  14. Singh RB, Neki NS, Kartikey K, et al. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem 2003;246:75-82. DOI
  15. Porterfield LM. Why did the response to warfarin change? RN 2000;63:107.
  16. Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial. Neurology 2005;64:713-5. PubMed
  17. Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6. DOI
  18. Berman M, Erman A, Ben-Gal T, et al. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol 2004;27:295–9. PubMed
  19. Storch A, Jost WH, Vieregge P, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol 2007;64:938-44. DOI
  20. Digiesi V, Cantini F, Oradei A, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994;15 Suppl:s257-63. PubMed
  21. Yamagami T, Takagi M, Akagami H, et al. Effect of coenzyme Q10 on essential hypertension, a double blind controlled study. In: Folkers KA, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5. Amsterdam: Elsevier Science Publications, 19
  22. Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension (review). Cochrane Database Syst Rev 2009;(4):CD007435. PubMed
  23. Rosenfeldt, F. L., Haas, S. J., Krum, H., Hadj, A., Ng, K., Leong, J. Y., and Watts, G. F. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum.Hypertens. 2007;21(4):297-306. PubMed
  24. Stamelou, M., Reuss, A., Pilatus, U., Magerkurth, J., Niklowitz, P., Eggert, K. M., Krisp, A., Menke, T., Schade-Brittinger, C., Oertel, W. H., and Hoglinger, G. U. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, place DOI
  25. Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure. Heart Lung Circ. 2003;12:135-41.
  26. Gane, E. J., Weilert, F., Orr, D. W., Keogh, G. F., Gibson, M., Lockhart, M. M., Frampton, C. M., Taylor, K. M., Smith, R. A., and Murphy, M. P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C
  27. Lynch, D. R., Perlman, S. L., and Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010;67(8):941-947. PubMed
  28. Young, J. M., Florkowski, C. M., Molyneux, S. L., McEwan, R. G., Frampton, C. M., Nicholls, M. G., Scott, R. S., and George, P. M. A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the me
  29. Ishiyama, T., Morita, Y., Toyama, S., Yamagami, T., and Tsukamoto, N. A clinical study of the effect of coenzyme Q on congestive heart failure. Jpn.Heart J 1976;17(1):32-42. PubMed
  30. Matthews, P. M., Ford, B., Dandurand, R. J., Eidelman, D. H., O'Connor, D., Sherwin, A., Karpati, G., Andermann, F., and Arnold, D. L. Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology 1993;43(5
  31. Malm, C., Svensson, M., Sjoberg, B., Ekblom, B., and Sjodin, B. Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiol Scand. 1996;157(4):511-512. PubMed
  32. Singh, R. B., Wander, G. S., Rastogi, A., Shukla, P. K., Mittal, A., Sharma, J. P., Mehrotra, S. K., Kapoor, R., and Chopra, R. K. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc. PubMed
  33. Digiesi V, Cantini F, and Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Current Therapeutic Research 1990;47(5):841-845.
  34. Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-52.
  35. Alehagen U, Johansson P, Bjornstedt M, et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citi
  36. Ho MJ, Li EC, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2016 Mar 3;3:CD007435. doi: 10.1002/14651858.CD007435.pub3. PubMed
  37. Tabrizi R, Akbari M, Sharifi N, Lankarani KB, Moosazadeh M, Kolahdooz F, et al. The effects of coenzyme Q10 supplementation on blood pressures among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. PubMed
  38. Tsai IC, Hsu CW, Chang CH, Tseng PT, Chang KV. Effectiveness of coenzyme Q10 supplementation for reducing fatigue: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2022;13:883251. PubMed
  39. Yaghini O, Hoseini N, Ghazavi MR, et al. A comparative study on the efficacy of coenzyme Q10 and amitriptyline in the prophylactic treatment of migraine headaches in children: A randomized controlled trial. Adv Biomed Res 2022;11:43. PubMed
  40. Hansen KS, Mogensen TH, Agergaard J, et al. High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: A randomized, phase 2, crossover trial. Lancet Reg Health Eur 2022. PubMed

See these in context on the Coenzyme Q10 monograph →

Grape 34 references
  1. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung
  2. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
  3. Vaswani SK, Hamilton RG, Carey RN, et al. Anaphylaxis recurrent urticaria and angioedema from grape hypersensitivity. J Allergy Clin Immunol 1998;101:S31.
  4. Chevallier A. The Encyclopedia of Medicinal Plants. London, UK: Dorling Kindersley, Ltd., 1996.
  5. Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.. PubMed
  6. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  7. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  8. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B PubMed
  9. O'Byrne, D. J., Devaraj, S., Grundy, S. M., and Jialal, I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin.Nutr. 2002;76(6):1367-1374.
  10. Schaefer, E., Peil, H., Ambrosetti, L., and Petrini, O. Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittelforschun PubMed
  11. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  12. de Lange, D. W., Scholman, W. L., Kraaijenhagen, R. J., Akkerman, J. W., and van de Wiel, A. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur.J Clin.Invest 2004;34(12):818-824. PubMed
  13. Samet, J. M. and Coultas, D. B. Reduced forced vital capacity in California grape workers. What does it mean? Am Rev.Respir.Dis 1992;145(2 Pt 1):255-256. PubMed
  14. Gamsky, T. E., McCurdy, S. A., Samuels, S. J., and Schenker, M. B. Reduced FVC among California grape workers. Am Rev.Respir.Dis 1992;145(2 Pt 1):257-262. PubMed
  15. de Lange, D. W., Verhoef, S., Gorter, G., Kraaijenhagen, R. J., van de Wiel, A., and Akkerman, J. W. Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin.Exp.Res 2007;31(8):1308-1314 PubMed
  16. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
  17. Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., and Joseph, J. A. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-734. PubMed
  18. Ingersoll, G. L., Wasilewski, A., Haller, M., Pandya, K., Bennett, J., He, H., Hoffmire, C., and Berry, C. Effect of concord grape juice on chemotherapy-induced nausea and vomiting: results of a pilot study. Oncol.Nurs.Forum 2010;37(2):213-221. PubMed
  19. Oliveira-Freitas, V. L., Dalla, Costa T., Manfro, R. C., Cruz, L. B., and Schwartsmann, G. Influence of purple grape juice in cyclosporine bioavailability. J Ren Nutr. 2010;20(5):309-313. PubMed
  20. Hollis, J. H., Houchins, J. A., Blumberg, J. B., and Mattes, R. D. Effects of concord grape juice on appetite, diet, body weight, lipid profile, and antioxidant status of adults. J Am Coll.Nutr. 2009;28(5):574-582. PubMed
  21. Dohadwala, M. M., Hamburg, N. M., Holbrook, M., Kim, B. H., Duess, M. A., Levit, A., Titas, M., Chung, W. B., Vincent, F. B., Caiano, T. L., Frame, A. A., Keaney, J. F., Jr., and Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in
  22. Rabe, E., Stucker, M., Esperester, A., Schafer, E., and Ottillinger, B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur.J Vasc.Endovasc. PubMed
  23. Trotta, M., Cesaretti, M., Conzi, R., Derchi, L. E., and Borgonovo, G. Elderly male with mesogastric pain. Small bowel obstruction caused by an intact fresh grape. Ann.Emerg.Med 2011;58(4):e1-e2. PubMed
  24. McCurdy, S. A., Wiggins, P., Schenker, M. B., Munn, S., Shaieb, A. M., Weinbaum, Z., Goldsmith, D., McGillis, S. T., Berman, B., and Samuels, S. Assessing dermatitis in epidemiologic studies: occupational skin disease among California grape and tomato ha
  25. Winter, C. K. and Kurtz, P. H. Factors influencing grape worker susceptibility to skin rashes. Bull.Environ.Contam Toxicol. 1985;35(3):418-426. PubMed
  26. Yamasaki, R., Dekio, S., and Jidoi, J. Contact dermatitis from grape bud. Contact Dermatitis 1985;12(4):226-227. PubMed
  27. Cox, J. and Grigg, M. Small bowel obstruction by an intact grape. J Am Geriatr.Soc 1986;34(7):550. PubMed
  28. Faircloth, D. E. and Robison, W. J. Obstruction of the sigmoid colon by grape seeds. JAMA 11-27-1981;246(21):2430. PubMed
  29. Marguerie, C. and Drouet, M. [Occupational eosinophilic lung in a grape grower: role of sulfites]. Allerg.Immunol.(Paris) 1995;27(5):163-167.
  30. Brito, FF., Martinez, A., Palacios, R., Mur, P., Gomez, E., Galindo, P. A., Borja, J., and Martinez, J. Rhinoconjunctivitis and asthma caused by vine pollen: a case report. J Allergy Clin Immunol 1999;103(2 Pt 1):262-266. PubMed
  31. Ras RT, Zock PL, Zebregs YE, et al. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr 2013;110(12):2234-41. PubMed
  32. Berry AC, Nakshabendi R, Abidali H, et al. Adverse effects of grape seed extract supplement: A clinical case and long-term follow-up. J Diet Suppl. 2016;13(2):232-5. PubMed
  33. Martínez-Maqueda D, Zapatera B, Gallego-Narbón A, Vaquero MP, Saura-Calixto F, Pérez-Jiménez J. A 6-week supplementation with grape pomace to subjects at cardiometabolic risk ameliorates insulin sensitivity, without affecting other metabolic syndrome mark
  34. Moon SW, Shin YU, Cho H, Bae SH, Kim HK; and for the Mogen Study Group. Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy. Medicine (Baltimore) 2019;98(21):e15515. PubMed

See these in context on the Grape monograph →

Buckwheat 12 references
  1. Schiffner R, Przybilla B, Burgdorff T, et al. Anaphylaxis to buckwheat. Allergy 2001;56:1020-1. PubMed
  2. Lee SY, Lee KS, Hong CH, Lee KY. Three cases of childhood nocturnal asthma due to buckwheat allergy. Allergy 2001;56:763-6. PubMed
  3. Wieslander G, Norback D. Buckwheat allergy. Allergy 2001;56:703-4.
  4. Skrabanja V, Liljeberg Elmstahl HG, Kreft I, Bjorck IM. Nutritional properties of starch in buckwheat products: studies in vitro and in vivo. J Agric Food Chem 2001;49:490-6. PubMed
  5. Bijlani RL, Gandhi BM, Gupta MC, et al. Effect of whole buckwheat (Fagopyrum esculentum) flour supplementation on lipid profile & glucose tolerance. Indian J Med Res 1985;81:162-8.
  6. Fritz SB, Gold BL. Buckwheat pillow-induced asthma and allergic rhinitis. Ann Allergy Asthma Immunol 2003;90:355-8. PubMed
  7. Ihme, N., Kiesewetter, H., Jung, F., Hoffmann, K. H., Birk, A., Muller, A., and Grutzner, K. I. Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled c
  8. Archimowicz-Cyrylowska B and et al. Clinical effect of buckwheat herb, Ruscus extract and troxerutin on retinopathy and lipids in diabetic patients. Phytother Res 1996;10(659):62. DOI
  9. Cifuentes L, Mistrello G, Amato S, et al. Identification of cross-reactivity between buckwheat and coconut. Ann Allergy Asthma Immunol. 2015 Dec;115(6):530-2. PubMed
  10. De Maat-Bleeker F, Stapel SO. Cross-reactivity between buckwheat and latex. Allergy. 1998 May;53(5):538-9. PubMed
  11. Qiu J, Liu Y, Yue Y, Qin Y, Li Z. Dietary tartary buckwheat intake attenuates insulin resistance and improves lipid profiles in patients with type 2 diabetes: a randomized controlled trial. Nutr Res. 2016 Dec;36(12):1392-1401. PubMed
  12. Li L, Lietz G, Seal C. Buckwheat and CVD risk markers: a systematic review and meta-analysis. Nutrients. 2018;10(5). pii: E619. PubMed

See these in context on the Buckwheat monograph →

Beet 14 references
  1. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  2. Clifford T, Berntzen B, Davison GW, et al. Effects of beetroot juice on recovery of muscle function and performance between bouts of repeated sprint exercise. Nutrients 2016;8. pii: E506. PubMed
  3. Siervo M, Lara J, Ogbonmwan I, Mathers JC. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. J Nutr 2013;143:818-26. PubMed
  4. Clifford T, Howatson G, West DJ, Stevenson EJ. Beetroot juice is more beneficial than sodium nitrate for attenuating muscle pain after strenuous eccentric-bias exercise. Appl Physiol Nutr Metab. 2017;42(11):1185-1191. PubMed
  5. Clifford T, Bell O, West DJ, Howatson G, Stevenson EJ. The effects of beetroot juice supplementation on indices of muscle damage following eccentric exercise. Eur J Appl Physiol. 2016;116(2):353-62. PubMed
  6. Wylie LJ, Kelly J, Bailey SJ, et al. Beetroot juice and exercise: pharmacodynamic and dose-response relationships. J Appl Physiol (1985). 2013;115(3):325-36. PubMed
  7. Garnacho-Casta&ntilde;o MV, Palau-Salv&agrave; G, Cuenca E, et al. Effects of a single dose of beetroot juice on cycling time trial performance at ventilatory thresholds intensity in male triathletes. J Int Soc Sports Nutr. 2018;15(1):49. PubMed
  8. Rasica L, Porcelli S, Marzorati M, et al. Ergogenic effects of beetroot juice supplementation during severe-intensity exercise in obese adolescents. Am J Physiol Regul Integr Comp Physiol. 2018;315(3):R453-R460. PubMed
  9. Henrohn D, Bj&ouml;rkstrand K, Lundberg JO, et al. Effects of oral supplementation with nitrate-rich beetroot juice in patients with pulmonary arterial hypertension-results from BEET-PAH, an exploratory randomized, double-blind, placebo-controlled, crosso
  10. Serra-Payá N, Garnacho-Castaño MV, Sánchez-Nuño S, et al. The relationship between resistance exercise performance and ventilatory efficiency after beetroot juice intake in well-trained athletes. Nutrients 2021;13(4):1094. PubMed
  11. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  12. Hemmatinafar M, Zaremoayedi L, Koushkie Jahromi M, et al. Effect of Beetroot Juice Supplementation on Muscle Soreness and Performance Recovery after Exercise-Induced Muscle Damage in Female Volleyball Players. Nutrients 2023;15(17):3763. PubMed
  13. Lim SH, Bae S, Lee HS, Han HK, Choi CI. Effect of Betanin, the Major Pigment of Red Beetroot (Beta vulgaris L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes. Pharmaceuticals (Basel) 2023;16(9):1224. PubMed
  14. Oscherwitz M, Tamayo RM, Heudebert A, Centor R. A Case of Pseudo-Hematochezia from Beet Supplement Ingestion. Am J Med 2023;136(9):e177-e178. PubMed

See these in context on the Beet monograph →

Tocotrienols 4 references
  1. Mensink RP, van Houwelingen AC, Kromhout D, Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 1999;69:213-9. PubMed
  2. Baumann LS, Spencer JS. The effects of topical vitamin E on the cosmetic appearance of scars. Dermatol Surg 1999;25:311-5. PubMed
  3. Khoo TL, Halim AS, Zakaria Z, Mat Saad AZ, Wu LY, Lau HY. A prospective, randomised, double-blinded trial to study the efficacy of topical tocotrienol in the prevention of hypertrophic scars. J Plast Reconstr Aesthet Surg. 2011 Jun;64(6):e137-45. Epub 201 PubMed
  4. Slivka A, Rink C, Paoletto D, Sen CK. Platelet function in stroke/transient ischemic attack patients treated with tocotrienol. FASEB J. 2020;34(9):11838-11843. PubMed

See these in context on the Tocotrienols monograph →

Echinacea 51 references
  1. Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998;168:170-1. PubMed
  2. Mullins RJ. Allergic reactions to Echinacea. J Allergy Clin Immunol 2000;104:S340-341 (Abstract 1003).
  3. Chavez ML, Chavez PI. Echinacea. Hosp Pharm 1998;33:180-8.
  4. Grimm W, Muller HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections. Am J Med 1999;106:138-43. PubMed
  5. Taylor JA, Weber W, Standish L, et al. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. JAMA 2003;290:2824-30.. PubMed
  6. Luettig B, Steinmuller C, Gifford GE, et al. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 1989;81:669-75. PubMed
  7. Stimpel M, Proksch A, Wagner H, et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845-9. PubMed
  8. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  9. Gallo M, Sarkar M, Au W, et al. Pregnancy outcome following gestational exposure to echinacea: A prospective controlled study. Arch Intern Med 2000;160:3141-3. PubMed
  10. Soon SL, Crawford RI. Recurrent erythema nodosum associated with echinacea herbal therapy. J Am Acad Dermatol 2001;44:298-9. PubMed
  11. Mullins RJ, Heddle R. Adverse reactions associated with echinacea: the Australian experience. Ann Allergy Asthma Immunol 2002;88:42-51. PubMed
  12. Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9.
  13. Schulten B, Bulitta M, Ballering-Bruhl B, et al. Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial. Arzneimittelforschung 2001;51:563-8.. PubMed
  14. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
  15. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med 2004;164:1237-41. PubMed
  16. Gorski JC, Huang S, Zaheer NA, et al. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo.Clin Pharmacol Ther 2003;73 (Abstract PDII-A-8):P94. PubMed
  17. Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol 2004;140:723-7. PubMed
  18. Goel V, Lovlin R, Barton R, et al. Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 2004;29:75-83.
  19. Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine 2003;10:66-86. PubMed
  20. Huntley AL, Thompson Coon J, Ernst E. The safety of herbal medicinal products derived from Echinacea species: a systematic review. Drug Saf 2005;28:387-400. PubMed
  21. Turner RB, Bauer R, Woelkart K, et al. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005;353:341-8.
  22. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  23. Perri D, Dugoua JJ, Mills E, Koren G. Safety and efficacy of echinacea (Echinacea augustafolia, e. purpurea and e. pallida) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e262-7.
  24. Kocaman O, Hulagu S, Senturk O. Echinacea-induced severe acute hepatitis with features of cholestatic autoimmune hepatitis. Eur J Intern Med 2008;19:148. PubMed
  25. Barrett B, Brown R, Rakel D. et al. Echinacea for treating the common cold: a randomized trial. Ann Intern Med 2010;153:769-77. PubMed
  26. Press Release: Echinacea herbal products should not be used in children under 12 years old. Medicines and Healthcare Products Regulatory Agency (UK). August 20, 2012. Available at: www.mhra.gov.uk/NewsCentre/Pressreleases/CON180627. (Accessed 21 October
  27. Barrett B, Brown R, Rakel D, Rabago D, et al. Placebo effects and the common cold: a randomized controlled trial. Ann.Fam.Med 2011;9:312-22. PubMed
  28. Haller J, Freund, TF, Pelczer, KG, et al. The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers. Phytother.Res. 2013;27:54-61.
  29. Grbic J, Wexler I, Celenti R, et al. A phase II trial of a transmucosal herbal patch for the treatment of gingivitis. J Am Dent.Assoc. 2011;142:1168-75. PubMed
  30. Schapowal A, Berger D, Klein P, et al. Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a randomized double-blind trial. Eur.J Med Res 9-1-2009;14:406-12. PubMed
  31. Bossaer JB and Odle BL. Probable etoposide interaction with Echinacea. J.Diet.Suppl 2012;9:90-5.
  32. Abdul MI, Jiang X, Williams KM, et al. Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. Br J Clin.Pharmacol. 2010;69:508-15. PubMed
  33. Kemp, D. E. and Franco, K. N. Possible leukopenia associated with long-term use of echinacea. J Am Board Fam.Pract. 2002;15(5):417-419.
  34. Liatsos, G., Elefsiniotis, I., Todorova, R., and Moulakakis, A. Severe thrombotic thrombocytopenic purpura (TTP) induced or exacerbated by the immunostimulatory herb Echinacea. Am J Hematol. 2006;81(3):224.
  35. Penzak, S. R., Robertson, S. M., Hunt, J. D., Chairez, C., Malati, C. Y., Alfaro, R. M., Stevenson, J. M., and Kovacs, J. A. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy s
  36. Maskatia, Z. K. and Baker, K. Hypereosinophilia associated with echinacea use. South.Med J 2010;103(11):1173-1174. PubMed
  37. Parnham MJ. Benefit-risk assessment of the squeezed sap of the purple coneflower (Echinacea purpurea) for long-term oral immunostimulation. Phytomed 1996;3:95-102. PubMed
  38. Schroder-Aasen T, Molden G, Nilsen OG. In vitro inhibition of CYP3A4 by the multiherbal commercial product Sambucus Force and its main constituents Echinacea purpurea and Sambucus nigra. Phytother Res 2012;26(11):1606-13.
  39. Moltó J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 2011;55(1):326-30.
  40. Goey AK, Meijerman I, Rosing H, et al. The effect of Echinacea purpurea on the pharmacokinetics of docetaxel. Br J Clin Pharmacol 2013;76(3):467-74.
  41. Moltó J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients. Antimicrob Agents Chemother 2012;56(10):5328-31. PubMed
  42. Lawrenson JA, Walls T, Day AS. Echinacea-induced acute liver failure in a child. J Paediatr Child Health 2014;50(10):841.
  43. Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008;103:445-9.
  44. Gabranis I, Koufakis T1, Papakrivos I, Batala S. Echinacea-associated acute cholestatic hepatitis. J Postgrad Med. 2015;61(3):211-2. PubMed
  45. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  46. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev.2014;(2):CD000530. doi: 10.1002/14651858.CD000530.pub3. PubMed
  47. Hoban CL, Byard RW, Musgrave IF. Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015. J Integr Med. 2019;17(5):338-343. PubMed
  48. Ogal M, Johnston SL, Klein P, Schoop R. Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial. Eur J Med Res. 2021 Apr 8;26(1):33. PubMed
  49. Lopresti AL, Smith SJ. An investigation into the anxiety-relieving and mood-enhancing effects of Echinacea angustifolia (EP107 &trade;): A randomised, double-blind, placebo-controlled study. J Affect Disord 2021;293:229-237.
  50. Weishaupt R, Buchkov A, Kolev E, Klein P, Schoop R. Reduction of viral load in patients with acute sore throats: Results from an observational clinical trial with Echinacea / Salvia lozenges [published online ahead of print, 2023 Mar 8]. Complement Med Re
  51. Sumer J, Keckeis K, Scanferla G, et al. Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial. Front Med (Lausanne) 2023;10:948787. PubMed

See these in context on the Echinacea monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team